Based on data from the Centers for Disease Control and Prevent, approximately 61 million Americans suffer from cardiovascular disease(s). Cardiovascular diseases include a number of disorders, including high blood pressure, coronary heart disease (heart attack, chest pain), stroke, congestive heart failure and defects of the heart and blood vessels.
Coronary artery disease, a form of cardiovascular disease (CVD), is a major cause of death in the United States today. Cerebrovascular disease is believed to be the third. The casual link of both coronary artery and cerebrovascular diseases is related to atherosclerosis. Atherosclerosis is the major cause of the more than one million heart attacks, approximately 400,000 strokes that occur each year and numerous vascular circulation problems. Many patients also suffer from hypertension.
There is a causal relationship between hypercholesterolemia and premature atherosclerosis. Increased levels of plasma cholesterol, primarily low density lipoproteins (LDL) and triglycerides, the greater the risk of subsequent heart attack. Events that appear to lead to atherosclerosis include the formation of lesions (artheromas) in carotid, coronary, and cerebral arteries, and in the aorta. These fatty deposits of cholesterol and cholesteryl ester that are found principally within the smooth muscle cells and macrophages of the intimal layer.
The development of atherosclerosis and cardiovascular disease are modulated by, and/or associated with, LDL oxidation, cyclo-oxygenase (COX) activity, lipoxygenase (LOX) activity, nitric oxide (NO) production, and nitric oxide synthase (NOS) activity. LDL oxidation is involved in the initiation of lesions (atheromas) which occur when macrophages take up oxidatively modified LDL and transform into so-called “foam cells”. The enzymes COX and LOX are involved in the arachidonic acid pathway which leads to the production of prostaglandins and thromboxane A2. Thromboxane A2 is known to cause vasoconstriction and platelet aggregation, and thus enhances the progression of atherosclerosis. Nitric oxide is known to inhibit platelet aggregation, monocyte adhesion/chemotaxis and proliferation of vascular smooth muscle, all of which are considered to be responsible for progression of atherosclerosis.
The lipids in blood plasma that are of major clinical importance are cholesterol and triglycerides. Cholesterol is always present as an ingredient in atherosclerotic plaque, along with fatty acid esters of cholesterol, phosphatids, neutral fats and dihydrocholesterol. Cholesterol is not miscible with water. To transport cholesterol in the blood, it is combined or repackaged with a protein. The combination of cholesterol and protein is called a lipoprotein. Very low-density lipoproteins (VLDL or pre-beta-lipoproteins), carry endogenously-synthesized triglycerides, which are removed by muscle, heart, adipose tissue, and other sites. Major remnants of VLDL metabolism are low-density lipoproteins (LDL or beta-lipoproteins). LDLs are catabolized by a mechanism involving receptors in cell membranes, but the major organ binding sites besides the liver are not well defined. It is the LDLs which contain the greatest percentage of cholesterol. These particles, when in excess in the blood, are deposited in the tissues and form a major part of the build-up in the arterial wall to form atherosclerotic plaque which narrows the channels of the coronary arteries which furnish the major blood supply to the heart muscle. High density lipoproteins (HDL or alpha-lipoproteins) contain phospholipids and cholesterol complexed with apolipoproteins, the bulk of which differ from those found in VLDLs and LDLs. It is the HDLs which contain the greatest amount of protein and the smallest amount of cholesterol and are believed to take cholesterol away from cells and transport it back to the liver for processing or removal.
Consequently, elevated blood cholesterol is a major risk factor for coronary heart disease, and many studies have shown that the risk of CHD events can be reduced by lipid-lowering therapy. Prior to the introduction of “statins” lipid-lowering methods were limited essentially to a low saturated fat and cholesterol diet, bile acid sequestrants (cholestyramine and colestipol), nicotinic acid (niacin), fibrates and probucol.
“Statins” are a class of drugs that lowers the level of cholesterol in the blood by reducing the production of cholesterol by the liver. Statins block the enzyme in the liver that is responsible for making cholesterol. This enzyme is called hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase for short). Therefore, statins are referred to as HMG-CoA reductase inhibitors.
There are currently five statin drugs on the market in the United States and include Lovastatin (Mevacor), Simvastatin (Zocor), Pravastatin (Pravachol), Fluvastatin (Lescol) and Atorvastatin (Lipitor). These drugs lower cholesterol by slowing down the production of cholesterol and by increasing the liver's ability to remove the LDL-cholesterol already in the blood.
Since statins have been introduced into the marketplace, certain side effects have been noted. The most common side effects include nausea, diarrhea, constipation and muscle aches. However, a more serious side effect includes a decrease in the body's supply of coenzyme Q10 (CoQ10), which is an essential nutrient for heart strength and function. Additionally, elevated liver enzymes have been noted in some individuals due to the statin.
Another serious side effect due to administration of statins is known as “Statin myopathy”. Statins can cause muscle pain and tenderness referred to as statin myopathy. In severe cases, muscle cells can break down (rhabdomyolysis) and release a protein called myoglobin into the bloodstream. Myoglobin can impair kidney function and lead to kidney failure. Certain drugs when taken with statins can increase the risk of rhabdomyolysis. These drugs include gemfibrozil, erythromycin (Erythrocin), antifungal medications, nefazodone (Serzone), cyclosporine and niacin.
Tangentially, insulin resistance syndrome commonly precedes type 2 diabetes and both disorders are associated with increased risk of heart disease. Insulin resistance is generally defined as an impaired ability of insulin to stimulate glucose uptake and lipolysis and to modulate liver and muscle lipid metabolism. In animals and humans, insulin resistance syndrome leads to hyperinsulinemia and to various defects in lipid metabolism such as enhanced secretion of atherogenic, triacylglycerol-rich very low-density lipoproteins (VLDL), increased liberation of nonesterified fatty acids (NEFA) from adipose tissue and increased accumulation of triacylglycerols in the liver. Other metabolic defects associated with insulin resistance include impairment of endothelium-dependent vasodilation. This last abnormality is largely a consequence of reduced bioavailability of nitric oxide, an important biological mediator involved in protection against atherosclerosis.
As a consequence of the general populations' problems with cardiovascular disease, atherosclerosis, insulin resistance, hyperinsulinemia and/or hypercholesterolemia, there is a need in the art for compositions address one or more of these conditions. Additionally, there is a need for a composition that can help to reduce cholesterol and/or triglycerides from blood plasma without one or more of the disadvantages noted with current drug therapies.